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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01AG053838 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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This study aims to investigate the impact of menopause-related sleep fragmentation on metabolic biomarkers of body fat gain. The investigators hypothesize that experimental sleep fragmentation will result in an adverse leptin response as a metabolic biomarker for body fat gain.
While obesity is highly prevalent in midlife and older women, with rates increasing markedly after age 40 and body fat increasing in half of women during and after the menopause transition, factors causing these changes are not well understood. Reduced total sleep time has been shown to adversely impact biomarkers of obesity, but the effect of the highly prevalent menopause-related sleep fragmentation secondary to hot flashes on metabolism and eating behaviors in humans is not known. We will use experimental paradigms to isolate the impact of menopause-related sleep disruption, as well as that of hot flashes and estrogen withdrawal, metabolic biomarkers of body fat gain and on eating behaviors, results of which will inform strategies to prevent body fat gain and improve cardio-metabolic health outcomes in women.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study arm | Experimental | Participants completed 2 nights of unfragmented sleep followed by 3 nights of experimentally-fragmented sleep during high estradiol (E2) phase of their menstrual cycle (Sleep Block 1). A subset of participants repeated these procedures in an experimentally-induced low-E2 state (Sleep Block 2). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Estradiol withdrawal | Drug | one injection of open-label intramuscular dose of leuprolide (3.75-mg depot), a gonadotropin-releasing hormone agonist that rapidly suppresses estradiol and temporarily achieves ovarian suppression. |
| Measure | Description | Time Frame |
|---|---|---|
| Normalized Serum Leptin Levels | 12-hr overnight fasted AM (morning) blood samples were assayed for leptin levels on study days 2-6 under both estrogenized and estradiol-withdrawal conditions [total: 10 samples]. For each individual, leptin values were normalized relative to the mean baseline leptin value. Baseline was defined as the unfragmented estrogenized condition (avg. of study days 2-3 in the estrogenized condition). | pre/post sleep fragmentation (3 days); pre/post estradiol withdrawal (~5 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Normalized Satiety Scores | 12-hr overnight fasted AM satiety scores were collected on study days 2-6 under both estrogenized and estradiol-withdrawal conditions [total: 10 scores]. For each individual, satiety scores were normalized relative to the mean baseline satiety score. Baseline was defined as the unfragmented estrogenized condition (avg. of study days 2-3 in the estrogenized condition). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hadine Joffe, MD MSc | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham & Women's Hospital | Boston | Massachusetts | 02115 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Study Arm | All participants who initiated Sleep Block 1 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sleep Block 1 |
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| Sleep Block 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Baseline Study Arm | All participants who completed Sleep Block 1 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Normalized Serum Leptin Levels | 12-hr overnight fasted AM (morning) blood samples were assayed for leptin levels on study days 2-6 under both estrogenized and estradiol-withdrawal conditions [total: 10 samples]. For each individual, leptin values were normalized relative to the mean baseline leptin value. Baseline was defined as the unfragmented estrogenized condition (avg. of study days 2-3 in the estrogenized condition). | To compare between study conditions, leptin levels [12-hr overnight fasted AM samples] were averaged across 2 samples [on study days 2-3] before 2 nights of sleep fragmentation and across 3 samples [on study days 4-6] after 3 nights of sleep fragmentation. Leptin levels were averaged across 5 samples [on study days 2-6] ~1 week before leuprolide administration (pre-estradiol withdrawal) and across 5 samples [on study days 2-6] ~4 weeks after leuprolide administration (post-estradiol withdrawal) | Posted | Mean | Standard Error | percentage of mean baseline leptin | pre/post sleep fragmentation (3 days); pre/post estradiol withdrawal (~5 weeks) |
|
4 months
Since participants received interventions simultaneously, it was not possible to attribute adverse events to any one intervention. Therefore, adverse events are presented for the larger group of all participants who initiated study procedures.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Participants | All participants who initiated study procedures | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hadine Joffe, MD MSc | Brigham and Women's Hospital | 617-732-4906 | hjoffe@bwh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 3, 2024 | Feb 9, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 3, 2024 | Feb 9, 2024 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 31, 2023 | Apr 25, 2024 | ICF_003.pdf |
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| ID | Term |
|---|---|
| D012892 | Sleep Deprivation |
| D015430 | Weight Gain |
| ID | Term |
|---|---|
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| D016729 | Leuprolide |
| ID | Term |
|---|---|
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
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|
| Fragmented sleep | Other | Fragmented sleep will be experimentally induced. |
|
| pre/post sleep fragmentation (3 days); pre/post estradiol withdrawal (~5 weeks) |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 | Sleep Fragmentation - Active | Participants after 3 nights of experimentally-fragmented sleep Fragmented sleep: Fragmented sleep will be experimentally induced. |
| OG001 | Sleep Fragmentation - Control | Participants after 2 nights of unfragmented sleep |
| OG002 | Estradiol Withdrawal - Active | Participants after experimentally-induced hypo-estradiol Estradiol withdrawal: one injection of open-label intramuscular dose of leuprolide (3.75-mg depot), a gonadotropin-releasing hormone agonist that rapidly suppresses estradiol and temporarily achieves ovarian suppression. |
| OG003 | Estradiol Withdrawal - Control | Participants during high-estradiol phase of menstrual cycle |
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| Secondary | Normalized Satiety Scores | 12-hr overnight fasted AM satiety scores were collected on study days 2-6 under both estrogenized and estradiol-withdrawal conditions [total: 10 scores]. For each individual, satiety scores were normalized relative to the mean baseline satiety score. Baseline was defined as the unfragmented estrogenized condition (avg. of study days 2-3 in the estrogenized condition). | To compare between study conditions, satiety scores [12-hr overnight fasted AM satiety scores] were averaged across 2 scores [on study days 2-3] before sleep fragmentation and across 3 scores [on study days 4-6] after 3 nights of sleep fragmentation. Satiety scores were averaged across 5 scores [on study days 2-6] ~1 week before leuprolide administration (pre-estradiol withdrawal) and across 5 scores [on study days 2-6] ~4 weeks after leuprolide administration (post-estradiol withdrawal). | Posted | Mean | Standard Error | percentage of mean baseline satiety | pre/post sleep fragmentation (3 days); pre/post estradiol withdrawal (~5 weeks) |
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| 41 |
| 0 |
| 41 |
| 32 |
| 41 |
| Gastrointestional disturbance | Gastrointestinal disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Nausea/vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Skin discomfort/irritation | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Respiratory infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Amenorrhea | Reproductive system and breast disorders | Non-systematic Assessment |
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| Menstrual | Reproductive system and breast disorders | Non-systematic Assessment |
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| Vasomotor symptoms | Reproductive system and breast disorders | Non-systematic Assessment |
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| IV discomfort/irritation | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | Non-systematic Assessment |
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| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001523 | Mental Disorders |
| D001836 | Body Weight Changes |
| D001835 | Body Weight |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| Superiority |